Revw4

Ancient-Modern Concordance in Ayurvedic Plants: Some Examples

Sukh Dev
University of Delhi, B.R.A. Centre for Biomedical Research, Delhi, India

folklore or traditional system of medicine of

Ayurveda is the ancient (before 2500 BLC.) Indian sytem of health care and longvity. It involves a one culture or another. Some examples are
holistic view of man, his health, and illness. Ayurvedic treatment of a disease consists of salubrious codeine, ephedrine, quinine, and emetine
use of drugs, diets, and certain practices. Medicinal preparations are invariably complex mixtures, among the traditional molecular drugs;
based mosdy on plant products. Around 1,250 plants are currently used in various Ayurvedic reserpine, artemisinin, and podophyllotoxin
preparations. Many Indian medicinal plants have come under scientdfic scrutiny since the middle (lead structure) from the period after the tra-
of the nineteenth century, although in a sporadic fashion. The first significant contibution from ditional molecular drug era; and garlic, gin-
Ayurvedic materia medica came with the isolation of the hypertesive alkaloid from the sarpgd- seng and St. John's wort of the currently
ha plant (Rauwo4Sa srpentina), valued in Ayurveda for the treatment of hypertension, mnia, popular herbal drugs. Thus, this paper high-
and insanity. This was the first important ancient-modem concordance in Ayurvedic plants. With lights the modern drug discovery potential
the gradual coming of age of chemistry and biology, disciplines central to the study of biologic of the plants described in various traditional
activities of natural products, many Ayurvedic plants have been reinvestigated. Our work on systems of medicine or in the folklore of var-
Commiphora wighti gum-resin, valued in Ayurveda for correcting lipid disorders, has been ious countries, which has been previously
described in some detail; based on these investigations, a modem antihyperlipoproteinemic drg is emphasized (3,9-12). It is with this back-
on the market in India and some other countries. There has also been concordance for a few other ground that I would like to discuss the
Ayurvedic crude drugs such as Asparagzu rcemosues Cedrw deodara, and Psoraea coryhflk KIey potential of and opportunity in Ayurvedic
work. y-aminobutyric acid, antihyperlipoproteinemic drug, Asparagus racemosus, Ayurveda, materia medica. However, it seems appropri-
bakuchiol, Cedrus dkodara Commiphora wighsti GABA, guggulsterones, himachalol, Psora/ca ate to briefly describe Ayurveda for those not
corylifolia, reserpine, Rauwo4fia serpentina. Environ Health Perspect 107:783-789 (1999). familiar with this Indian heritage.
[Online 25 August 1999]
htp:/llehpnetls.niebs. gov/does/l999/107p7ni3-783-78.9devabstr html Ayurveda
The origin of Ayurveda has been lost in pre-
historic antiquity, but its characteristic con-
In the early development of modern medi- pharmacies during the period 1959-1980 cepts appear to have matured between 2500
cine, biologically active compounds from contained plant extracts or active principles and 500 B.C. in India. The word "Ayurveda"
higher plants have played a vital role in pro- derived therefrom (4). Even now, 75-80% of is derived from "ayus (r)," meaning life, and
viding medicines to combat pain and diseases. the world population depends on crude plant "veda," meaning knowledge; thus, Ayurveda
For example, in The British Pharmacopoeia of drug preparations to treat their health prob- literally means "science of life." It is the
1932 (1), over 70% of organic monographs lems, although this may be mostly because of ancient Indian system of health care and
were on plant-derived products. However, economic considerations. longevity. Ayurveda takes a holistic view of
with the advent of synthetic medicinals, and In the last two decades, there has been a man, his health, and illness. It aims at posi-
subsequently of antibiotics, the role of plant- new trend in the preparation and marketing tive health, which has been defined as a well-
derived therapeutic agents significantly of drugs based on medicinal plants (3,5-8). balanced metabolism coupled with a healthy
dedined (mostly) in the economically devel- These preparations, labeled herbal drugs or state of being. Disease, according to
oped nations. Thus, in the 1980 edition of phytomedicines, are single plant extracts or Ayurveda, can arise from the body and/or
the The British Pharmacopoeia (2), the share fractions thereof and are distinct from the the mind because of external factors or
of plant-based monographs fell to approxi- pure chemical entities of molecular drugs intrinsic causes. Ayurvedic treatment is
mately 20%. In terms of new chemical enti- (3). These new plant-derived products are aimed at the patient as an organic whole,
ties introduced as medicinal agents over the carefully standardized, and their efficacy and
past several decades, the share of plant-based safety for a specific application have been Address correspondence to S. Dev, University of
drugs has been no more than 2% (3). demonstrated. The present global market for Delhi, B.R.A. Centre for Biomedical Research,
However, plant-derived medicinals continue these products has been estimated to be Delhi 110 007, India. Telephone: 91 (011)
to occupy an important niche in the treat- approximately $20 billion U.S. and is grow- 7256245. Fax: 91 (011) 7257730. E-mail: ssda@
ment of diseases worldwide. Thus, most of ing at the rate of 15-20% annually (3). ndf.vsnl.net.in
the recently introduced plant-based drugs Thus, plant-based therapeutic agents con- The research presented in this paper is the result
of investigations carried out by several students,
have been innovative in character and repre- tinue to have scientific, social, and commer- whose names appear in the appropriate references; I
sent outstanding contributions to therapeu- cial significance and appear to be gathering a thank all of them for their dedication and work. I
tics. These drugs include several anticancer momentum in health-relevant areas. also thank U.R. Nayak; R. Srivastava; B. Bhatt; N.
agents such as podophyllotoxin, paclitaxel, A study of the process by which the tra- Nand, S. Nityanand, and their colleagues (Central
camptothecin, or compounds based on these ditional or more recent plant-based molecu- Drug Research Institute, Lucknow, India); I.
as lead structures; each of these classes of lar drugs or the new breed of herbal drugs Kawada (Takasago Research Institute, Tokyo,
came to be used in present-day medicine Japan); K. Jeevaratnam (Defence Research
compounds exhibit their anticancer activity Development Establishment, Gwalior, India); and
by distinct mechanisms (3). It has been esti- reveals that, in over 70% of the cases, the R. Misra and J. Cott (National Institute on Aging,
mated that in the United States, 25% of all starting point has been some reference to the National Institutes of Health, Bethesda, MD).
prescriptions dispensed from community use of that plant as an indigenous cure in a Received 27 October 1998; accepted 5 May 1999.

Environmental Health Perspectives * Volume 107, Number 10, October 1999 783
Reviews * Dev

and treatment consists of salubrious use of 470 medicinal plants (19). Other than these account ofearly research covering the period
drugs, diets, and certain practices (13). monumental treatises, many (> 70) Nighantu up to theearly 1930s was incorporated into
Ayurveda has a vast literature in Sanskrit Granthas (pharmacy lexicons) were written, book form (26), and this book was revised
and various Indian languages, covering vari- mostly between the seventh and sixteenth and updated in 1958 (27). In 1961, the
ous aspects of diseases, therapeutics, and phar- centuries (13,16). Raj Nighantu by Narhari Central Council of Ayurvedic Research,
macy. It has evolved its own theoretical base, Pandita and Madanpala Nighantu by Government of India, arranged a conference
which is difficult to comprehend in terms of Madanpala are considered masterpieces on of reputed Ayurvedic physicians to prepare a
modern scientific concepts, at least at present. medicinal plants (12. list of the most useful Ayurvedic plants. Thus,
However, here we are concerned only with All ancient texts on Ayurveda divide a list of 190 single plant drugs emerged. This
the exploration of its materia medica. medical knowledge into eight branches was followed-up by the formulation of a com-
Pharmaceutics occupies an important (Ashtanga), and this is no different from the posite drug research scheme by the Ministry
place in Ayurveda. Medicinal preparations are contemporary approach. Also, Ayurvedic of Health, in collaboration with the Indian
complex mixtures including plant- and ani- descriptions of diseases are much like the Council of Medical Research and the Council
mal-derived products, minerals, and metals. modern delineation (20). Plant-derived of Scientific and Industrial Research. The aim
Plants form a dominant part of Ayurvedic drugs have been categorized according to of this scheme was to indude prominent sci-
pharmacopoeia. The earliest references to their pharmacologic/therapeutic action. For entists of the country involved in both
such plants are found in the Rig Veda and the example, in the Charaka Samhita, drugs Ayurvedic and modern dinical practice, phar-
Atharva Veda, dating back to the second mil- were classified into 50 groups (Table 1) (21). macology, pharmacognosy, and chemistry in
lennium B.C. The Charaka Samhita (- 900 Ayurveda, in its prime, was a cogent, sci- an effort to evaluate the classical claims in
B.C.) (14,15) is the first recorded treatise filly entifically organized discipline. Ayurvedic terms of contemporary scientific knowledge.
devoted to the concepts and practice of texts were much respected in neighboring Results of these investigations have been sum-
Ayurveda; its primary focus was therapeutics. countries, as evidenced from their translation marized (28,29).
This work listed 341 plants and plant prod- into Greek (300 B.C.), Tibetan and Chinese Two other major screening programs
ucts for use in medicine. The next landmark (300 A.D.), Persian and Arabic (700 A.D.), were launched around 1964, one at the
in Ayurvedic literature was the Sushruta and several languages of other Asian people Central Drug Research Institute (CDRI),
Samhita (- 600 B.C.) (16,17), which has spe- (22,23). Currently, Ayurveda is widely prac- Lucknow, India (30), and the other at Ciba-
cial emphasis on surgery. It described 395 ticed in the Hindustan peninsula (India and Geigy Research Centre, Mumbai, India (31).
medicinal plants, 57 drugs of animal origin, the neighboring countries) and, in recent Both of these programs covered the Indian
and 64 minerals and metals as therapeutic years, has attracted much attention in eco- flora in general, without reference to any use
agents. Sushruta, the father of surgery, lived nomically developed countries such as those of these plants in Ayurveda or in any Indian
and practiced surgery in Varanasi, India, in Europe and in the United States and folklore. The outcome of the Ciba-Geigy pro-
approximately 2,500 years ago. Another Japan (24). gram has not been made public. On the other
important authority in Ayurveda was hand, the CDRI effort, spanning a period of
Vagbhatta of Sind, in present day Pakistan, Ayurvedic Drugs 20 years, covered over 2,500 plants that were
who practiced around the seventh century There are approximately 1,250 Indian medic- screened for a variety of biologic activities.
A.D. His work Ashtanga Hridaya is considered inal plants (25) that are used in formulating Interesting leads were apparently obtained,
unrivaled for the principles and practice of therapeutic preparations according to and these results have been summarized (32).
medicine (13,18). The Madhava Nidana Ayurvedic or other traditions. Several of these Indian medicinal plants have been stud-
(- 800-900 A.D.) was the next important plants came under the contemporary (mod- ied in various universities and research insti-
milestone; it is the most famous Ayurvedic ern) scientific scrutiny since the middle of the tutes; this work is still in progress, with
work on the diagnosis of diseases (16). The nineteenth century. A fairly comprehensive results being reported in professional journals.
last celebrated writer on Hindu medicine was
Bhava Mishra of Magadha, whose treatise Table 2. Some Ayurvedic crude drugs that have received pharmacologic and clinical support for their
Bhava Prakasha, written around 1550, is held therapeutic claims.
in high esteem by modern Ayurvedic practi- Plant Active Type of activity
tioners for its descriptions of approximately Botanical name Sanskrit name component (references)
Table 1. Classification of plant drugs according to Acorus calamus Vacha Unknown Tranquilizer (28)
Charaka Samahita (21).a Adhatoda zeylanica Vasa Vasicine Bronchodilator, oxytocic (35)
Aloe vera Kumaari Unknown Antiinflammatory (36-35)
No. Sanskrit name Use Andrographis paniculata Bhuinimba Andrographolide Hepatoprotector (39,40)
1 Jivaniya Promoting longevity Asparagus racemosus Shatavari Shatavarn-1 Antiabortifacient (41-43)
3 Lekhaniya Antiobesity Azadirachta indica Nimb Gedunin Antimalarial (44,45)
6 Dipaniya Promotor of digestion Bacopa monneri Brahmi Baccosides Improves memory (46)
7 Balya Promoting strength Boerhaa via diffusa Punarnava Unknown Diuretic, antiinflammatory (28)
8 Varnya Promoting complexion Boswellia serrata Sallakee Boswellic acids Antiarthritic (47,48)
15 Krmighna Anthelmintic Butea frondosa Palasha Palasonin Anthelmintic (28,49)
17 Stanyajanana Galactagogue Cedrus deodara Devadaru Himachalols Spasmolytic (50,51)
23 Vamanopaga Emetic Centella asiatica Mandookpaarni Asiaticosides Skin diseases, psychotropic (28,52)
24 Virechanopaga Purgative Commiphora wightti Guggulu Gugguisterones Hypolipidemic (53-55)
35 Mutravirechaniya Diuretic Curcuma longa Haridra Curcumin Antiinflammatory (48,56)
36 Kasahara Antitussive Holarrhena antidysenterica Kutaja Conessine Antidysenteric (29)
38 Svayathuhara Antiinflammatory Phyllanthus niruri Bhoomyaamalakee Unknown Hepatoprotector (57,55)
39 Jvarahara Febrifuge Picrorrhiza kurroa Katukaa Picroside, kutcoside Hepatoprotector (59-62)
47 Vedanasthapana Analgesic Psoralea corylifolia Bakuchi Psoralen, bakuchiol Antileucoderma, antibacterial (25)
50 Vayahsthapana Antiaging Rauwolfia serpentina Sarpagandha Reserpine Tranquilizer (63,64)
Listing is only partial. Swertia chirata Kairata Unknown Hepatoprotector (65,66)

784 Volume 107, Number 10, October 1999 * Environmental Health Perspectives

Two publications (33,34) have attempted to
cover these findings.
In a significant number of cases, current
data from these and other studies corroborate
the main claims of these plants according to
traditional use. Some examples are shown in
Table 2 (35-66). This concordance is mean-
ingftl; to emphasize its scientific, commercial,
and social potential, I would like to elaborate
on some of these examples.
Psoralea corylifolia (bakuchi). This is an
erect annual found almost throughout India.
Its seed powder is valued in Ayurveda for the
treatment ofvitiligo, psoriasis, and inflamma-
tory diseases of the skin (67). Chemical and
pharmacologic investigations (29,68,69) led
to the isolation of the active principle, pso-
ralen (Figure 1), in the mid-1930s; psoralen
has been shown to stimulate the formation of
melanin (70). Psoralen is used therapeutically
for the treatment of leucoderma. More recent
investigations have led to the isolation of the
Figure 1. Diagrams of various chemical compounds present in some useful Ayurvedic plants.
Environmental Health Perspectives * Volume 107, Number 10, October 1999
Reviews * Modern-ancient concordance in Ayurvedic plants
meroterpene bakuchiol (Figure 1) (71-73)
and other related compounds (74).
Bakuchiol has been shown to posses potent
antibacterial activity (29) and is useful for the
treatment of psoriasis (75). Recently, baku-
chiol has been shown to be a DNA poly-
merase inhibibitor (76).
Rauwolfia serpentina (sarpagandha).
This is a famous Ayurvedic plant because it
represents the earliest (- 1950) contribution
of Ayurveda to modern drug development.
Rauwolfia serpentina received international
attention and rekindled the interest of
researchers in exploring higher plants for
innovative leads. Roots of this plant are val-
ued in Ayurveda for the treatment of hyper-
tension, insomnia, and insanity (63); in
Hindi speaking areas, this plant is called
"pagle ki booti" (plant for the insane).
Significant pharmacologic, clinical, and
chemical work on the plant carried out in
India attracted the attention of the CIBA
group (Basel, Switzerland), who finally suc-
ceeded (in 1952) in isolating the sedative
principle, reserpine, a minor alkaloidal con-
stituent. Reserpine was introduced in the
market in 1953 and was heralded as a revolu-
tionary event in the treatment of hyperten-
sion, as it had the twin effect of lowering
high blood pressure and acting as a tranquil-
lizer (64).
Asparagus racemosus (shatavari). Roots
of Asparagus racemosus are reputed in
Ayurveda as galactagogue, and preparations
based on this drug (e.g., Shatavari sidh ghrit)
are often recommended in cases of threatened
abortion (28,7X). This plant contains several
glycosides, and one of these, shatavaran-I
(Figure 1) (41,42, has been shown to block
oxytocin-induced contractions in rat, guinea
pig, and rabbit uteri in vivo and in situ (78).
Galactagogue activity has also received some
experimental support (43).
Cedrus deodara (devadaru). Wood of the
Himalayan cedar has several medicinal attrib-
utes, and preparations based on this plant are
used to treat cough, bronchitis, and skin dis-
eases, among others (79). An oil obtained
from the wood is used in villages for treating
insect infestations on animals; there is suffi-
cient experimental support for this (80). The
essential oil of the wood has been thoroughly
examined chemically (81-83). Himachalol
(Figure 1), one of the constituents of the
essential oil, has been shown to possess potent
spasmolytic activity (50,51). Activity-guided
fractionation led to the identification of
himachalenes (Figure 1) as the antimange
compounds. A commercial preparation
(Flematic) based on this finding is being mar-
keted (84) in India as a broad spectrum agent
against various types of ectoparasites that
commonly affect animals.
Commiphora wightti (guggulu).
Commiphora wightti is another significant
contribution of Ayurveda to modern medi-
cine. Commiphora wightti is a small tree
belonging to the family Burseraceae; when
injured, the plant exudes a yellowish gum
resin that soon solidifies to an agglomerate of
tears or stalactitic pieces with balsamic odor.
This gum resin ("guggulu" in Sanskrit) is
renowned in Ayurveda for the treatment of
inflammatory disorders, rheumatoid arthritis,
lipid disorders, obesity, skin diseases, and
other ailments (85). Some of these claims
appeared to be supported by the results of
pharmacologic screening (53,86-89) carried
out during 1960-1969 on the crude drug. In
Sushruta Samhita, the description of medoro-
ga (obesity and associated lipid disorders) is
quite reminiscent of the modern concepts of
pathogenesis of atherosclerosis (Figure 2)
(90), and guggulu was recommended for
treatment. In 1969, few drugs with useful
hypolipidemic activity were on the market.
785
Reviews * Dev

Bioassay-guided separation eventually led, in a significant enhancement in the level of the The discovery of antihyperlipoproteinemic
1971, to the isolation and characterisation of desired high-density lipoproteins and reduc- guggulsterones in the guggulu resin was an
two antihyperlipoproteinemic compounds, Z- tion in the unwanted low-density lipids (99). event of considerable interest because these
guggulsterone and E-guggulsterone (Figure 1) Gugulipid also caused regression of atheroma- compounds represent a new structural type in
(54,55). Both compounds have similar activi- tous lesions induced in rabbits by a fat-rich hypolipidaemic agents (103). Consequently, a
ty comparable (Table 3) to that of clofibrate diet. Gugulipid has a multifocal action: it number of pregnane derivatives were synthe-
(Figure 1), a synthetic hypolipemic drug that inhibits cholesterol biosynthesis, mobilizes fat sized and evaluated for their hypolipemic
became available on the market in 1967. from tissues, and increases secretion of bile activity. One of these (code no. 81/574) was
Guggulu gum resin essentially consists of acids (100-IOZ). Although gugguisterones are found to be at least as active as guggulsterones
an ethyl acetate-soluble fraction ( 45%) and pregnane derivatives, they are completely and is currently undergoing clinical trials (99).
an insoluble carbohydrate gum (- 55%). The devoid of any estrogenic, antiestrogenic, or
latter is toxic to rats and is devoid of any progestational activity. Gugulipid was deared Additional Concordance
hypolipemic activity. The desired biologic for registration in India in 1986, and the drug In recent years we have studied several groups
activity lies entirely in the ethyl acetate-soluble has been manufactured and marketed in India of Ayurvedic plants by modern in vitro meth-
fraction. This fraction has been extensively since 1987. Gugulipid is now being sold in the ods, in coiloboration with various groups. A
chemically examined (54, 91-9) and consists international market. brief account of these investigations follows.
of diterpenoids, triterpenoids, steroids, lig-
nans, fatty tetrol esters, etc. A review of this Table 3. A comparison of cholesterol-lowering activity of guggulsterones, clofibrate, and some guggulu
work has been published (98). Approximately fractions in rats.
4% of the active guggulsterones are present in Product Percent lowering of serum lipids Percent inhibition of
this fraction. However a comparison (Table 3) (100 mg/kg, Normal rats Rats fed high fat cholesterol biosynthesis
of the activity of this fraction with that of pure oral for 30 days) Cholesterol Triglycerides Cholesterol Triglycerides in rat liver homogenate
guggulsterones showed a vastly disproportion- Ethyl acetate soluble 34 24 46 24 30
ate activity for the total extract, possibly due to (gugulipid)
synergistic or additive activity of some of the Guggulsteronesa 35 28 48 29 35
components of the mixture (12). In view of Total ketonesb 30 26 29 20 22
this, further development of the product (col- Nonketonicb 15 16 25 15 10
Clofibrate 43 30 - - 40
lecting pharmacologic, biochemical, toxicolog-
ic, teratogenic, mutagenic, and dinical data) Data from Nand (991.
'Mixture of Z- and E-guggulsterone isomers (80:20). 1'These represent ketonic and nonketonic fractions of the neutral cut
was carried out on a standardized ethyl acetate of the total ethyl acetate-soluble portion of the gum resin (15).
extract, code-named gugulipid, containing at
least 4% guggulsterones. Gugulipid exhibits a Table 4. Lipid-lowering activity of gugulipid
dose-dependent lowering of serum cholesterol Percent change in serum lipoproteins
and triglycerides in normal and hyperlipidem- Test system LDL VLDL HDL
ic rats, rabbits, and monkeys. A study of the
lipoprotein profile in rabbits (Table 4) showed Hyperlipemic rabbits 50 mg/kg P.0./90 days -25 -27 +29
Normal monkeys 60 mg/kg P.0/90 days -50 -30 -

Abbreviations: HDL, high density lipoprotein; LDL, low density lipoprotein; VLDL, very low density lipoprotein.
Ancient Modern Data from Nand (99).

Table 5. Modern scientific evaluation of some Ayurvedic memory-enhancing and antiaging plants.
Plant Enzyme inhibition (%) Receptor binding (%)
(Sanskrit name) ACE AChE NMDA GABA (A/B) NGF
1 Acorus calamus - - - - -
(vaccha)
Benincasa hispida - - - - -
(kooshmand)
Celastrus paniculatus NI NI -
'I, (jyotishmati)
Centella asiatica - - - 82 (B)
(mandookpaarni)
Convolvulus microphyllus - - 55 - High
(shankhapushpi)
Nardostachysjatamansi - 90 -
(jataamansi)
Ocimum gratissimum 68 - NI
Many complications Many complications (tulsi)
Pluchea lanceolata 60 - - 99 (B) 50
(raasna)
Terminalia chebula 82 - 53 53 (B) -
(haritaki)
Figure 2. Analogy drawn between the modern Withania somnifera NI NI - > 80 (A,B)
concept of pathogenesis of atherosclerosis and (ashwagandha)
the ancient concept of the pathogenesis of obesity Abbreviations: AChE, acetylcholine esterase; ACE, angiotensin-converting enzyme; GABA (AB), y-aminobutyric acid; NGF,
and associated lipid disorders. Definitions: shlesh- nerve growth factor; NI, not investigated; NMDA, N-methyl-D-aspartic acid. The appropriate plant part, as recommended
malahara, rich food (fats, proteins); vata vikaras, in Ayurveda, was extracted with methanol by room temperature percolation. For biological screening, the methanol-free
diseases of the nervous system. extract was taken up in aqueous DMSO to get 5 pg of the material/mL.

786 Volume 107, Number 10, October 1999 * Environmental Health Perspectives

Learning, memory, and cognitive disor-
ders. This area of research was selected for
three reasons: a) there is a paucity of modern
drugs/agents facilitating acquisition, reten-
tion, and retrieval of information and knowl-
edge; b) with the increasing number of elder-
ly people in the world population, the need
for drugs to treat cognitive disorders, such as
senile dementia and Alzheimer disease, have
acquired special urgency; and c) Ayurveda
claims that several plants, the so-called "med-
hya" plants, possess such activities.
The past two decades have seen tremen-
dous advances in the area of brain physiology,
learning, memory, and various brain disor-
ders, and a host of mechanisms at molecular
level have been delineated (104-106).
Synapses-the junctions of nerve cells repre-
senting the basic interactive unit of neuronal
circuits-constitute the fundamental sys-
temic relationship within the brain.
Understanding how this interactive multi-
tude of neuronal circuitry is established ini-
tially, and refined continuously throughout
life, is fundamental to understanding the
molecular basis of learning and memory. At
present, an impressive array of chemical enti-
ties affecting synapse formation, neuronal
differentiation, neurotransmission, nerve
growth and repair, and several other func-
tions are recognized. Approximately 50 neu-
rotransmitters belonging to diverse chemical
groups have been identified in the brain
(107). Receptors, which are activated by
these chemicals, assume special importance in
the present context. Specifically, N-methyl-
D-aspartic acid (NMDA) and y-aminobutyric
acid (GABA) receptors have been implicated
in learning and memory (108-111). It has
been further postulated that GABAB antago-
nists may enhance memory (108), whereas
the NMDA receptor has the ability to medi-
ate synaptic plasticity (111). Acetylcholine,
the first neurotransmitter to be characterized,
has a very significant presence in the brain;
recently, Winkler et al. (112) determined
that acetylcholine is essential for learning and
memory. Acetylcholine has been a special tar-
get for investigations for almost two decades
because its deficit, among other factors, has
been held responsible for senile dementia and
other degenerative cognitive disorders,
including Alzheimer disease (113-116).
Approximately 5% of the neurons in the
Table 6. Cholecystokinin (peripheral) receptor
binding assay of triphala components
Plant Percent inhibition
Terminalia chebula 96
Terminalia bellerica 91
Emblica officinalis 76
The dried kernel-free fruits were extracted with methanol
by room temperature percolation. For biological screen-
ing, the methanol-free extract was taken up in aqueous
DMSO to get 5 pg of the material/mL.
Environmental Health Perspectives * Volume 107, Number 10, October 1999
Reviews * Modern-ancient concordance in Ayurvedic plants
hippocampus (the part of the brain central to
learning, memory, and emotions) disappears
with each decade after 50 years of age, and
the brain tries to compensate for this by fur-
ther growth of the neurites (neuron axon and
dendrites) (117), which are vital for normal
functioning of the brain. Thus, nerve growth
factor has an important role to play. Several
reports have suggested that angiotensin-con-
verting enzyme inhibitors (e.g., captopril)
may indirectly lead to improved cognitive
performance (116). There are several other
factors [e.g., gonadal steroid receptors
(118,119], that have a bearing on learning
and memory, but they are not relevant to the
current work.
The knowledge about neurotransmitters,
enzymes, growth factors relevant to memory
and learning, and cognitive disorders is
already being used for the discovery and
development of suitable therapeutic agents
(120,121). Major emphasis has been on
acetylcholine. Because the number of acetyl-
choline receptors dedines with advancing age,
inhibitors of acetylcholine esterase (AChE),
which terminates the action of acetylcholine,
have been special targets for development.
We studied some of the Ayurvedic plants
reputed to be memory enhancers (medhya)
and antiaging drugs (Vayahsthapana) by
standard receptor binding and enzyme inhi-
bition techniques (Table 5), with the specific
aim of identifying any leads based on the
above considerations. It was gratifying to see
several positive results. Shankhapushpi (leaf
is one of the prime medhya plants of
Ayurveda; it may be useful for neural regen-
eration and synaptic plasticity. Jataamansi
(rhizome) appears to be an excellent candi-
date for a potential inhibitor of AChE.
Haritaki (fruit) is highly prized in Ayurveda
for antiaging; its extract has displayed several
activities. Ashwagandha (root) is another
important antiaging plant. We have investi-
gated this plant in some detail because its
extract showed high affinity for both GABAA
and GABAB receptors. Receptor-binding
assay-guided fractionation of the crude
methanol extract resulted in a butanol frac-
tion with retention of GABAB receptor activ-
ity [concentration that inhibits 50% (IC50) -
47 pg/mL] and an aqueous fraction that
retained both GABAA (IC50 0.37 pg/mL)
- (Mumbai, India) had devised a system for
and GABAB (IC50 15.8 pg/mL) affinities.
- screening plant extracts that may promote
Table 7. Angiogenesis assay (chorioallantoic membrane assay).
Botanical Sanskrit
Embellica officinalis Amalaki
Hedychium spicatum Shati
Hemidesmus indicus Saariva
Nardostachys jatamaansi Jataamaansi
Nigella sativa Krishna jeeraka
Saussurea lappa Kushth
Gastrointestinal disorders, satiety and
feeding behavior. Cholecystokinin (CCK) is
a polypeptide hormone, widely distributed in
the gastrointestinal tract and nervous system
(both peripheral and central); it plays a major
role in the digestive process. CCK also occurs
in the brain, where it acts as a neurotransmit-
ter and neuromodulator. CCK exists as sever-
al different molecular species: CCK-58,
CCK-39, CCK-33, CCK-8, and CCK-4.
The octapeptide CCK-8, for example, pre-
dominates in the brain. Also, there are at least
two types of CCK receptors (122-124).
Over the past 10-15 years, there has
been much activity in the development of
potent and selective CCK agonists and
antagonists because these agents may lead to
novel therapy for the treatment of disorders
such as gastrointestinal disturbances, pancre-
atitis, gastric and pancreatic carcinomas,
obesity, and cognition dysfunction, in which
CCK has been implicated. Several such mol-
ecules are under active development (124).
There are also satiety agents, fashioned after
CCK, which may fight obesity (125).
It seemed worthwhile to evaluate the
three components of Triphala (three fruits),
an Ayurvedic remedy for treating various gas-
trointestinal disorders. The three fruits are
products of Terminalia chebula (Sanskrit: har-
itaki), Terminalia bellerica (bibhitaka), and
Emblica officinalis (aamalaki); haritaki has also
been recommended in Ayurveda for treat-
ment of obesity. The methanol-extracted
material from the three fruits was evaluated in
vitro by radioligand binding assays (Table 6)
(126). As is evident from these data, the three
extracts showed good affinity for the CCK
receptor, thus, offering good opportunity for
the isolation and evaluation of new and possi-
bly clinically useful ligands. My laboratory
investigated the extract from T bellerica in
some detail and isolated several pure com-
pounds, one of which (code name B3EA-10;
melting point 190-192°C) showed high
affinity (IC50 1.8 pg/ mL).
-
Hair growth promoting activity. A num-
ber of plants have been recommended in the
Ayurvedic system for promoting the growth
of head hair, as distinct from the treatment of
alopecia, male pattern baldness. Because the
research division of Hindustan Lever
Plant part Results
Fruit
Root New growth
Root Bundling and new growth
Root New growth
Seed
Root Bundling and new growth
787
Reviews * Dev
hair growth, I sent them extracts of plants
selected on the basis of claims of hair growth
in the traditional medicine literature. The
test system is based on the premise that trans-
port of nourishment to the hair root, the site
of biochemical activity, would be facilitated
by strengthening the hair root system. For
this they used the chicken chorioallantoic
membrane assay, a model for angiogenesis
(neovascularization). Normally, angiogenesis
is unimportant except during growth and
wound healing, and researchers have been
seeking inhibitors of angiogenesis in search of
anticancer compounds (127). However, my
interest was to see if any of the traditional
plants promote neovascularization because
this would aid blood supply to the hair papilla.
Table 7 summarizes these investigations; sev-
eral positive results are evident.
Conclusion
The materia medica of Ayurveda, and other
similar repositories of knowledge from other
cultures, represent a valuable resource for
development of not only medicinal prepara-
tions but also nutraceuticals and cosmaceuti-
cals according to modern-day requirements.
However, these claims must be critically eval-
uated in terms of modern scientific parame-
ters. When such a project is envisaged, some
prerequisites must be met. It is important to
carefully correlate the disease description in
the ancient literature with the modern etiolo-
gy and clinical picture to ensure correct cor-
respondence. In the Ayurvedic literature,
there was much stress on the collection of
plant material during a particular season,
from a particular locale, and at a certain time
of day. It is now well established that the
concentration and profile of secondary
metabolites in a plant depend on environ-
mental, nutritional, and and photoperiodici-
ty factors. Thus, the correct type of plant
material is essential. Because traditional plant
preparations have significant historical back-
ground, it may be ethical to clinically evalu-
ate these first and then collect modern toxi-
cologic data. For herbal preparations, it may
not be essential to pinpoint the active princi-
ple(s), but it is desirable to have this informa-
tion. In any case, important classes of com-
pounds essential for biologic activity must be
delineated. All of this knowledge will be
essential for proper standardization of a prod-
uct. If a product is too complex, it must be
standardized in terms of biologic activity
parameters. This will require much research
effort.
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